Cr. Logg et al., A uniquely stable replication-competent retrovirus vector achieves efficient gene delivery in vitro and in solid tumors, HUM GENE TH, 12(8), 2001, pp. 921-932
A major obstacle in cancer gene therapy is the limited efficiency of in viv
o gene transfer by replication-defective retrovirus vectors in current use.
One strategy for circumventing this difficulty would be to use vectors cap
able of replication within tumor tissues, We have developed a replication-c
ompetent retrovirus (RCR) vector derived from murine leukemia virus (MuLV).
This vector utilizes a unique design strategy in which an Internal ribosom
e entry site-transgene cassette is positioned between the env gene and the
3' long terminal repeat (LTR). The ability of this vector to replicate and
transmit a transgene was examined in culture and in a solid tumor model in
vitro. The RCR vector exhibited replication kinetics similar to those of wi
ld-type MuLV and mediated efficient delivery of the transgene throughout an
entire population of cells in culture after an initial inoculation with 1
plaque-forming unit (PFU) of vector per 2000 cells. After injection of 6 x
10(3) PFU of vector into established subcutaneous tumors, highly efficient
spread of the transgene was observed over a period of 7 weeks, in some case
s resulting in spread of the transgene throughout the entire tumor. MuLV-ba
sed RCR vectors show significant advantages over standard replication-defec
tive vectors in efficiency of gene delivery both in culture and in vitro. T
his represents the first example of the use of an RCR vector in an adult ma
mmalian host, and their first application to transduction of solid tumors.